Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders

@article{Akbarian2006MolecularAC,
  title={Molecular and cellular mechanisms of altered GAD1/GAD67 expression in schizophrenia and related disorders},
  author={Schahram Akbarian and Hsien-Sung Huang},
  journal={Brain Research Reviews},
  year={2006},
  volume={52},
  pages={293-304}
}
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Further correlation and validation work between brain regions, cerebrospinal fluid and peripheral blood expression profiling are required to provide a better understanding of GAD25 and GAD67.
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Understanding of altered CpG methylation, hydroxymethylation, and active DNA demethylation provide a framework for the identification of new targets, which may be exploited for the pharmacological intervention of the psychosis associated with SZ and possibly BP+.
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The findings suggest that GABA transmission is decreased in the cerebellar cortices in individuals with schizophrenia and additional gene expression changes may reflect an attempt to increase GABA neurotransmission at the Cerebellar glomerulus.
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A large preclinical and cognitive literature suggests that a dysfunctional frontal GABAergic network is associated to abnormal electroencephalographic spectra, which are thought to underlie higher cognitive functions and are known to be disturbed in schizophrenia.
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GAD1 mRNA Expression and DNA Methylation in Prefrontal Cortex of Subjects with Schizophrenia
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Results suggest that chromatin remodeling mechanisms are involved in dysregulated GABAergic gene expression in schizophrenia, with a significant, on average 8-fold deficit in repressive chromatin-associated DNA methylation at the promoter.
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An extensive characterization of the GAD67 deficit in schizophrenia is provided, and novel evidence of a functional impairment in PV neurons that may underlie cognitive deficits is provided.
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The results support the importance of genetic variation in GAD1 and COMT in regulating prefrontal cortical GABA function, and the directionality of the effects is inconsistent with earlier evidence of decreased GABA activity in schizophrenia.
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References

SHOWING 1-10 OF 129 REFERENCES
GAD67 and GAD65 mRNA and protein expression in cerebrocortical regions of elderly patients with schizophrenia
TLDR
A substantial dysregulation of GAD mRNA expression in schizophrenia is suggested and, taken together with the results of protein expression studies, raise the possibility that both cortical and subcortical GABA function may be compromised in the disease.
GABAergic dysfunction in schizophrenia and mood disorders as reflected by decreased levels of glutamic acid decarboxylase 65 and 67 kDa and Reelin proteins in cerebellum
GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss
TLDR
Quantitative trait TDT analyses showed an intriguing association between several SNPs and increased rate of frontal gray matter loss, suggesting that the gene encoding GAD67 may be a common risk factor for schizophrenia.
Polymorphisms in glutamate decarboxylase genes: analysis in schizophrenia
TLDR
Although the results are negative, this was the first study to investigate GAD genes in schizophrenia, and further studies of these genes, particularly with schizophrenia subtypes, may prove valuable.
Decrease in reelin and glutamic acid decarboxylase67 (GAD67) expression in schizophrenia and bipolar disorder: a postmortem brain study.
TLDR
The selective down-regulation of RELN and GAD(67) in prefrontal cortex of patients with schizophrenia and bipolar disorder who have psychosis is consistent with the hypothesis that these parameters are vulnerability factors in psychosis; this plus the loss of the correlation between these 2 parameters that exists in nonpsychotic subjects support the hypotheses that these changes may be liability factors underlying psychosis.
Relationship of Brain-Derived Neurotrophic Factor and Its Receptor TrkB to Altered Inhibitory Prefrontal Circuitry in Schizophrenia
TLDR
Investigating the involvement of signaling mediated by brain-derived neurotrophic factor (BDNF) and its receptor tyrosine kinase TrkB in producing the altered GABA-related gene expression in schizophrenia found decreased TrkB signaling appears to underlie the dysfunction of inhibitory neurons in the PFC of subjects with schizophrenia.
GAD67: the link between the GABA-deficit hypothesis and the dopaminergic- and glutamatergic theories of psychosis
TLDR
Pharmacological principles that raise GAD67 expression levels could represent novel targets for antipsychotic therapy and could be a surrogate marker for psychosis liability.
An association study between polymorphisms in five genes in glutamate and GABA pathway and paranoid schizophrenia
An epigenetic mouse model for molecular and behavioral neuropathologies related to schizophrenia vulnerability
TLDR
The inhibition of histone deacetylases could represent a pharmacological intervention mitigating epigenetically induced vulnerability to schizophrenia in individuals at risk.
Differential hippocampal expression of glutamic acid decarboxylase 65 and 67 messenger RNA in bipolar disorder and schizophrenia.
TLDR
The hypothesis that the expression of the 2 isoforms of GAD, 65 kd and 67 kd, is differentially affected in the hippocampus in schizophrenia and bipolar disorder is tested and a region-specific deficit of G AD(65) and GAD(67) mRNA expression is found in bipolar disorder.
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